Intramural Visualization of Scroll Waves in the Heart

Abstract

Despite extensive research, the fundamental biophysical mechanisms underlying severe heart rhythm disorders such as ventricular fibrillation remain poorly understood. Ventricular fibrillation is an acute and highly lethal medical condition, in which the heart's electrical system, which normally activates the contractions of the cardiac muscle, becomes highly disorganized and ineffective in orchestrating the orderly beating of the heart. Understanding the nature of the underlying abnormal electrical activity is thought to be key to the development of novel diagnostic and therapeutical strategies in treating cardiac arrhythmias. However, current imaging technology provides only very limited insight into the complex spatial-temporal electrical patterns underlying ventricular fibrillation within the heart muscle. In this work, a novel imaging approach is presented, which aims at imaging both electrical and elasto-mechanical activity of the cardiac muscle during cardiac tachyarrhythmias to better understand the correlation of electrical activity and resultant mechanical deformation and to explore the possibility to infer the electrical activity from the mechanical deformation. The work includes computational modeling and data analysis as well as ex vivo imaging experiments with isolated, intact hearts. Using mathematical concepts from nonlinear physics that describe universal pattern formation processes in excitable electrical systems such as the heart, the imaging experiments were guided and potential interpretations and methods for processing of data were validated. It was found that both electrical and elasto-mechanical activity of the cardiac muscle are highly correlated during ventricular tachycardia and fibrillation. For instance, rotating electrical activity, which was filmed on the surface of the fibrillating, contracting heart using fluorescence imaging, was found to induce similarly rotating rate of deformation patterns. Moreover, the rotating elasto-mechanical patterns could simultaneously be imaged within the heart wall using ultrasound. The data suggests that the rotational mechanical patterns are the finger-print of electrical spiral and scroll wave activity during cardiac fibrillation. In computer simulations, it was found that the core regions of spiral and scroll waves can similarly be described by electrical or elasto-mechanical lines of phase singularity, the electrical lines of phase singularity corresponding to electrical scroll vortex wave filaments and the mechanical lines of phase singularity corresponding to topological defect lines that arise in the dynamic elasto-mechanical deformation patterns resulting from the rapid fibrillatory activity of the cardiac muscle. Both the experimental and numerical findings suggest that a mechanical measurement can provide insight into the organizational structure of ventricular fibrillation throughout the volume of the heart muscle tissue. Next to these findings, the development of the methodological approach, including high-speed fluorescence imaging equipment and data processing techniques with which it is possible to perform imaging experiments with contracting cardiac tissue preparations, to perform simultaneous voltage, calcium and strain measurements as well as to perform imaging combined with intramural strain measurements using ultrasound, is the main result of this thesis. The findings presented in this thesis have important implications on potential future clinical applications.